Papillary thyroid cancer (PTC), whose incidence has been increasing in the last years, occurs more frequently in women. Experimental studies suggested that estrogen could be an important risk factor for the higher female incidence. In fact, it has been demonstrated that 17β-estradiol (E2) could increase proliferation and dedifferentiation in thyroid follicular cells. Genomic estrogen responses are typically mediated through classical estrogen receptors, the α and β isoforms, which have been described in normal and abnormal human thyroid tissue. Nevertheless, effects mediated through G protein estrogen receptor 1 (GPR30/GPER/GPER1), described in some thyroid cancer cell lines, could be partially responsible for the regulation of growth in normal cells. In this study, GPER1 gene and protein expression are described in non-malignant and in papillary thyroid cancer (PTC), as well as its association with clinical features of patients with PTC. The GPER1 expression was lower in PTC as compared to paired non-malignant thyroid tissues in fresh samples of PTC and in silico analysis of GEO and TCGA databases. In PTC cases of TCGA database, low GPER1 mRNA expression was independently associated with metastatic lymph nodes, female gender, and BRAF mutation. Besides, GPER1 mRNA levels were positively correlated with mRNA levels of thyroid differentiation genes. These results support the hypothesis that GPER1 have a role in PTC tumorigenesis and might be a potential target for its therapy. Further studies are needed to determine the functionality of these receptors in normal and diseased thyroid.

乳头状甲状腺癌 (PTC) 的发病率在过去几年一直在增加，在女性中更常见。实验研究表明，雌激素可能是女性发病率较高的一个重要危险因素。事实上，已经证明 17β-雌二醇 (E2) 可以增加甲状腺滤泡细胞的增殖和去分化。基因组雌激素反应通常通过经典的雌激素受体、α 和 β 同种型介导，它们已在正常和异常的人类甲状腺组织中进行了描述。然而，在某些甲状腺癌细胞系中描述的通过 G 蛋白雌激素受体 1 ( GPR30/GPER/GPER1 ) 介导的作用可能是调节正常细胞生长的部分原因。在这项研究中，GPER1在非恶性和乳头状甲状腺癌 (PTC) 中描述了基因和蛋白质表达，以及它与 PTC 患者临床特征的关联。与 PTC 新鲜样品和GEO 和 TCGA 数据库的计算机分析中的配对非恶性甲状腺组织相比，PTC 中的GPER1表达较低。在 TCGA 数据库的 PTC 病例中，低GPER1 mRNA 表达与转移性淋巴结、女性和 BRAF 突变独立相关。此外，GPER1 mRNA水平与甲状腺分化基因的mRNA水平呈正相关。这些结果支持GPER1的假设在 PTC 肿瘤发生中发挥作用，可能是其治疗的潜在靶点。需要进一步的研究来确定这些受体在正常和患病甲状腺中的功能。